Embryonic stem cells are derived from a four- or five-day-old human embryo that is in the blastocyst phase of development. The embryos are usually extras that have been created in IVF (in vitro fertilization) clinics where several eggs are fertilized in a test tube, but only one is implanted into a woman.

Sexual reproduction begins when a male’s sperm fertilizes a female’s ovum (egg) to form a single cell called a zygote. The single zygote cell then begins a series of divisions, forming 2, 4, 8, 16 cells, etc. After four to six days – before implantation in the uterus – this mass of cells is called a blastocyst. The blastocyst consists of an inner cell mass (embryoblast) and an outer cell mass (trophoblast). The outer cell mass becomes part of the placenta, and the inner cell mass is the group of cells that will differentiate to become all the structures of an adult organism. This latter mass is the source of embryonic stem cells – totipotent cells (cells with total potential to develop into any cell in the body).

Life size model of fetus at 8 weeks after conception, in hand of adult. Detailed coloring is not shown. This illustrates that fetus has all limbs formed at this stage, and shows size in comparison to that of adult.

In a normal pregnancy, the blastocyst stage continues until implantation of the embryo in the uterus, at which point the embryo is referred to as a fetus. This usually occurs by the end of the 10th week of gestation after all major organs of the body have been created.

However, when extracting embryonic stem cells, the blastocyst stage signals when to isolate stem cells by placing the “inner cell mass” of the blastocyst into a culture dish containing a nutrient-rich broth. Lacking the necessary stimulation to differentiate, they begin to divide and replicate while maintaining their ability to become any cell type in the human body. Eventually, these undifferentiated cells can be stimulated to create specialized cells.

Adult stem cells

Adult or somatic stem cells exist throughout the body after embryonic development and are found inside of different types of tissue. These stem cells have been found in tissues such as the brain, bone marrow, blood, blood vessels, skeletal muscles, skin, and the liver. They remain in a quiescent or non-dividing state for years until activated by disease or tissue injury.

Adult stem cells can divide or self-renew indefinitely, enabling them to generate a range of cell types from the originating organ or even regenerate the entire original organ. It is generally thought that adult stem cells are limited in their ability to differentiate based on their tissue of origin, but there is some evidence to suggest that they can differentiate to become other cell types.

Stem cell lines

Once stem cells have been allowed to divide and propagate in a controlled culture, the collection of healthy, dividing, and undifferentiated cells is called a stem cell line. These stem cell lines are subsequently managed and shared among researchers. Once under control, the stem cells can be stimulated to specialize as directed by a researcher – a process known as directed differentiation. Embryonic stem cells are able to differentiate into more cell types than adult stem cells.

Stem cell cultures

Stem cells are either extracted from adult tissue or from a dividing zygote in a culture dish. Once extracted, scientists place the cells in a controlled culture that prohibits them from further specializing or differentiating but usually allows them to divide and replicate. The process of growing large numbers of embryonic stem cells has been easier than growing large numbers of adult stem cells, but progress is being made for both cell types.

Potency

Stem cells are categorized by their potential to differentiate into other types of cells. Embryonic stem cells are the most potent since they must become every type of cell in the body. The full classification includes:

Unipotent – the ability to only produce cells of their own type, but have the property of self-renewal required to be labeled a stem cell. Examples include (adult) muscle stem cells.

Oligopotent – the ability to differentiate into a few cells. Examples include (adult) lymphoid or myeloid stem cells.

Multipotent – the ability to differentiate into a closely related family of cells. Examples include hematopoietic (adult) stem cells that can become red and white blood cells or platelets.

Pluripotent – the ability to differentiate into almost all cell types. Examples include embryonic stem cells and cells that are derived from the mesoderm, endoderm, and ectoderm germ layers that are formed in the beginning stages of embryonic stem cell differentiation.

Totipotent – the ability to differentiate into all possible cell types. Examples are the zygote formed at egg fertilization and the first few cells that result from the division of the zygote.

Embryonic stem cells are considered pluripotent instead of totipotent because they do not have the ability to become part of the extra-embryonic membranes or the placenta.

Research with stem cells

Scientists and researchers are interested in stem cells for several reasons. Although stem cells do not serve any one function, many have the capacity to serve any function after they are instructed to specialize. Every cell in the body, for example, is derived from first few stem cells formed in the early stages of embryological development. Therefore, stem cells extracted from embryos can be induced to become any desired cell type. This property makes stem cells powerful enough to regenerate damaged tissue under the right conditions.

Identification of stem cells

Although there is not complete agreement among scientists of how to identify stem cells, most tests are based on making sure that stem cells are undifferentiated and capable of self-renewal. Tests are often conducted in the laboratory to check for these properties.

One way to identify stem cells in a lab, and the standard procedure for testing bone marrow or hematopoietic stem cell (HSC), is by transplanting one cell to save an individual without HSCs. If the stem cell produces new blood and immune cells, it demonstrates its potency.

Clonogenic assays (a laboratory procedure) can also be employed in vitro to test whether single cells can differentiate and self-renew. Researchers may also inspect cells under a microscope to see if they are healthy and undifferentiated or they may examine chromosomes.

To test whether human embryonic stem cells are pluripotent, scientists allow the cells to differentiate spontaneously in cell culture, manipulate the cells so they will differentiate to form specific cell types, or inject the cells into an immunosuppressed mouse to test for the formation of a teratoma (a benign tumor containing a mixture of differentiated cells).

Brain disease treatment

Additionally, replacement cells and tissues may be used to treat brain disease such as Parkinson’s and Alzheimer’s by replenishing damaged tissue, bringing back the specialized brain cells that keep unneeded muscles from moving. Embryonic stem cells have recently been directed to differentiate into these types of cells, and so treatments are promising.

Organ and tissue regeneration

Tissue regeneration is probably the most important possible application of stem cell research. Currently, organs must be donated and transplanted, but the demand for organs far exceeds supply. Stem cells could potentially be used to grow a particular type of tissue or organ if directed to differentiate in a certain way. Stem cells that lie just beneath the skin, for example, have been used to engineer new skin tissue that can be grafted on to burn victims.

Blood disease treatments

Adult hematopoietic stem cells found in blood and bone marrow have been used for years to treat diseases such as leukemia, sickle cell anemia, and other immunodeficiencies. These cells are capable of producing all blood cell types, such as red blood cells that carry oxygen to white blood cells that fight disease. Difficulties arise in the extraction of these cells through the use of invasive bone marrow transplants. However hematopoietic stem cells have also been found in the umbilical cord and placenta. This has led some scientists to call for an umbilical cord blood bank to make these powerful cells more easily obtainable and to decrease the chances of a body’s rejecting therapy.

General scientific discovery

Stem cell research is also useful for learning about human development. Undifferentiated stem cells eventually differentiate partly because a particular gene is turned on or off. Stem cell researchers may help to clarify the role that genes play in determining what genetic traits or mutations we receive. Cancer and other birth defects are also affected by abnormal cell division and differentiation. New therapies for diseases may be developed if we better understand how these agents attack the human body.

Another reason why stem cell research is being pursued is to develop new drugs. Scientists could measure a drug’s effect on healthy, normal tissue by testing the drug on tissue grown from stem cells rather than testing the drug on human volunteers.

Cell deficiency therapy

Healthy heart cells developed in a laboratory may one day be transplanted into patients with heart disease, repopulating the heart with healthy tissue. Similarly, people with type I diabetes may receive pancreatic cells to replace the insulin-producing cells that have been lost or destroyed by the patient’s own immune system. The only current therapy is a pancreatic transplant, and it is unlikely to occur due to a small supply of pancreases available for transplant.

Stem cell controversy

The debates surrounding stem cell research primarily are driven by methods concerning embryonic stem cell research. It was only in 1998 that researchers from the University of Wisconsin-Madison extracted the first human embryonic stem cells that were able to be kept alive in the laboratory. The main critique of this research is that it required the destruction of a human blastocyst. That is, a fertilized egg was not given the chance to develop into a fully-developed human.

When does life begin?

The core of this debate – similar to debates about abortion, for example – centers on the question, “When does life begin?” Many assert that life begins at conception, when the egg is fertilized. It is often argued that the embryo deserves the same status as any other full grown human. Therefore, destroying it (removing the blastocyst to extract stem cells) is akin to murder. Others, in contrast, have identified different points in gestational development that mark the beginning of life – after the development of certain organs or after a certain time period.

Chimeras

People also take issue with the creation of chimeras. A chimera is an organism that has both human and animal cells or tissues. Often in stem cell research, human cells are inserted into animals (like mice or rats) and allowed to develop. This creates the opportunity for researchers to see what happens when stem cells are implanted. Many people, however, object to the creation of an organism that is “part human”.

Legal issues

The stem cell debate has risen to the highest level of courts in several countries. Production of embryonic stem cell lines is illegal in Austria, Denmark, France, Germany, and Ireland, but permitted in Finland, Greece, the Netherlands, Sweden, and the UK. In the United States, it is not illegal to work with or create embryonic stem cell lines. However, the debate in the US is about funding, and it is in fact illegal for federal funds to be used to research stem cell lines that were created after August 2001.

Basic concepts of stem cell science

Stem cells are unique cells within the body that continue to divide an produce either additional stem cells or cells that become specialized to function in the body

COMMENTARY: The structure of the body is made up of by billions of individual microscopic cells that work together to complete the functions necessary for life. Many cells of the adult body are specialized to complete unique functions, and if damaged may die contributing in symptoms of disease or injury. Other cells of the body retain the potential to replace dead cells. These cells known as stem cells are a focus of scientific research and ethical debate.

Development: During normal human development, all of the adult structures are ultimately formed from the products of the fertilized egg. At the most basic level, development consists of two fundamental processes.

Cells divide to create copies of themselves. The fertilized egg splits into two cells, those two cells divide into four cells, and process continues to generate the trillions of cells in the adult body. However, the body does not develop as a shifting, shapeless blob.

Instead, in the process of differentiation the cells acquire unique characteristics that allow them to complete special functions within the body. As the cells are generated, they begin to become specialized with some cells becoming basic tissues such as nerves and muscles and ultimately become arranged in the creation of functional organs such as the skin or stomach.

In truth, these two processes oversimplify the process since development from a fertilized egg into an adult is an incredibly complicated series of events, many of which are just now beginning to be understood. Further complicating normal development is that some stages must be completed properly at a specific time in order for the next step to occur. Birth defects are often caused by disruption of the normal process of develop by radiation, chemical teratogens, metabolic imbalances, or viruses. An example of this is Fetal Alcohol Spectrum Disorders occur when the unborn fetus is exposed to the toxic effects of alcohol during important developmental stages. The disruption and often death of cells can cause long-lasting, growth deficiencies and deficits in brain development. Removal of the toxic agents after the damage is done does not reverse the effects and it is not currently possible to replace the lost cells at a later time.

Stem cells are the unspecialized cells capable of dividing to maintain a reserve of unspecialized cells. More importantly some of the products of stem cell division are able to follow a path of specialization to become the functional cells needed by the body.

Adult Stem Cells: A basic understanding of stem cells has been around for decades. There are collections of adult stem cells located throughout the body. These cells are capable of being recruited when needed throughout an individual’s lifetime.

The classic example of an adult stem cell are the blood-forming (hematopoietic) stem cells found in bone marrow. In an adult, the red blood cells carrying oxygen throughout the body only live for about 120 days. The blood-forming stem cells continue to divide (maintaining a reserve of stem cells) but also produce cells that will become specialize by developing into the functional red blood cells. Without these stem cells the body would be unable to replace old or damaged red blood cells. The blood-forming stem cells can also develop into other types of blood cells. Bone marrow transplants have been used since 1968 to treat patients with diseases such as leukemia, immune deficiency disorders, or Hodgkin’s lymphoma. In essence, bone marrow transplants are the first example of adult stem cell treatment.

Scientists have identified and isolated Adult stem cells from many regions of the body including brain, muscle, skin, liver, ovary, and testes. These cells are important in the normal body and a greater understanding of their properties is improving the potential of using these cells in the treatment of diseases. However, these cells are not completely unspecialized and will only become a subset of adult cells. These adult stem cells cannot be used to repair or replace all regions of the body.

Embryonic Stem Cells: In the field of biomedical science, embryonic stem cells are the Holy Grail, sought after because of their immense potential. By definition, embryonic stem cells are isolated from cells of early embryos formed through in vitro fertilization. Most often these embryos were no longer needed and donated for research purposes rather than being destroyed. Since these cells come from embryos less than four to five days old, the cells are almost completely unspecialized.

Once isolated these embryonic stem cells are grown in the laboratory using the process of cell culture. By controlling the conditions the cells can be kept unspecialized and dividing. Scientists are now studying the factors involved in gradually and specifically directing these cells to differentiate into the functional cells of the adult body. Once these processes are better understood, it may be possible to create replacement cells, tissues or organs for therapeutic purposes.

Stem cells are basic cells that can become almost any type of cell in the body. Human stem cells can come from an embryo or an adult human. They have many possible uses in science and medicine, yet controversy surrounds them.

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